Numerous studies in mice have documented the existence of a severe age-related immunodeficiency plus a greatly increased incidence of autoimmunity. Many of the "diseases of aging" may be related to these dual manifestations of immune dysfunction. The same situation appears to obtain in man. Accordingly, it is planned to study age-related immune functional, genetic, and certain biochemical parameters in normal young-adult, middle-aged, moderately old, and over-90 year old humans and in populations of subjects with Down's Syndrome and systemic lupus erythematosus, which diseases may be considered "models" for accelerated aging. Particular focus will include: cellular immunity; suppressor and effector cells; T-cell subsets; mitogenic response; autoimmune status; alloantigens; lymphocyte membrane phenomena (micro-tubules); lymphocyte morphology by electron microscopy; lymphocyte biochemistry (cyclic nucleotides, amino acid transport, etc.); and lymphocyte DNA-excision repair capacity and mechanisms. Further evidence that Down's Syndrome and systemic lupus are associated with accelerated aging will be evaluated by these and other criteria. The subsequent 5-year mortality rates of the older portion of the normal and of Down's Syndrome populations will be correlated with their prior immune functional status.